Circadian pattern of ventilation during acute and chronic hypercapnia in conscious adult rats

Abstract

Seifert, Erin L., and Jacopo P. Mortola. Circadian pattern of ventilation during acute and chronic hypercapnia in conscious adult rats. Am J Physiol Regulatory Integrative Comp Physiol 282: R244-R251, 2002; 10.1152/ajpregu. 00290.2001.-Because metabolism is a determinant of the ventilatory chemosensitivity, we tested the hypothesis that the ventilatory response to acute and prolonged hypercapnia is adjusted to the circadian oscillations in oxygen consumption (V O2). Adult rats were instrumented for measurements of body temperature (Tb) and activity by telemetry. Pulmonary ventilation (V E) was measured by the barometric method and V O2 by the flow-through method. In the acute experiments, 16 conscious rats entrained to a 12:12-h light (L)-dark (D) cycle (lights on 7:00 AM) were exposed to air, 2%, and then 5% CO2 in normoxia (30-45 min each) at 11:00 AM and 11:00 PM. In a separate group of seven rats, simultaneous recordings of all variables were made continuously for 3 consecutive days in air followed by 3 days in 2% CO2 in normoxia, in a 12:12-h L-D cycle (lights on 7:00 AM). In air, all variables were significantly higher at night, whether rats were studied acutely or chronically. Acute CO2 exposure had similar significant effects at 11:00 AM and 11:00 PM on V E (ϳ25 and 100% increase with 2 and 5% CO2, respectively) and V O2 (ϳ8% drop with 5% CO2), such that the hyperventilatory response (% increase in V E/V O2 from air) was similar at both times. Chronic CO2 breathing increased V E at all times of the day, but less so during the L phase (ϳ15 vs. 22% increase in L and D, respectively), when activity was lower. However, V O2 was reduced from the air level (ϳ10% drop) in the L, such that the V E/V O2 response was similar between L and D. The same result was obtained when the V E/V O2 response was compared between the L and D phases for the same level of activity. These results suggest that, throughout the day, the hypercapnic hyperpnea, whether during acute or prolonged CO2, is perfectly adjusted to the metabolic level.control of breathing; chemosensitivity; barometric method; oxygen consumption IN MAMMALS AND BIRDS, blood gas homeostasis depends on the matching of pulmonary ventilation (V E) to metabolism. Indeed, a close coupling between V E and oxygen consumption (V O 2 ) has been found under a variety of conditions where V O 2 is either raised or lowered (20). Variations in metabolism are also associated with changes in V E chemosensitivity (19). A higher V O 2 , as during muscular exercise (35) or cold exposure (12), is accompanied by a greater absolute increase in V E in response to acute hypoxia or hypercapnia, whereas reflex hyperpnea is lower whenVO 2 is reduced, such as with myxedema (36) or semi-starvation (6). Hence, the V E chemoreflex response seems to track V O 2 . This would tend to minimize fluctuations in blood gases in normoxia and when chemosensory drive is elevated.Oxygen consumption presents a circadian oscillation. Although the daily high values of V O 2 generally occur when an animal i...

Breathing around the clock: an overview of the circadian pattern of respiration

“…Hence, the human V _ E response to acute CO 2 , similar to the HVR, presents a circadian pattern. This differs from the results of studies performed in rats, which, exposed to increased CO 2 twice a day, in the morning and the evening hours, responded with a similar hyperventilation (Peever and Stephenson 1997;Seifert and Mortola 2002b).…”

“…In rats exposed to 2-3% CO 2 for several days the increase in V _ E , when compared to the normocapnic values at the corresponding times of the day, was more pronounced in the dark phase (Seifert and Mortola 2002b). However, because in the L phase V _ O 2 dropped slightly, the degree of hypercapnic hyperventilation remained steady throughout the whole 24 h (Fig.…”

“…The blunting effects of hypoxia on the amplitude of the circadian pattern of T b and V _ O 2 occurred just as well in intact as in sino-aortic denervated animals, indicating that the action of hypoxia does not require the inputs from the peripheral chemoreceptors (Fenelon et al 2000). Furthermore, neither hyperoxia (40% O 2 ) nor hypercapnia (2-3% CO 2 in normoxia) had important effects on the circadian patterns of T b Seifert and Mortola 2002b), despite the fact that hyperoxia reduces the tonic activity of the peripheral chemoreceptors, and hypercapnia stimulates both peripheral and central chemoreceptors. In the only study performed on humans with a sustained increase of the inspired CO 2 (1% CO 2 for a few weeks), it was concluded that the circadian pattern of T b was not altered (Samel et al 1998).…”

Daily and seasonal rhythms in the respiratory sensitivity of red-eared sliders (Trachemys scripta elegans)

“…These oscillations in breathing were correlated to daily changes in metabolism and not to changes in chemosensitivity because the hyperventilatory response did not vary between day and night (i.e. there was no %⌬ACR between night and day) (Peever and Stephenson, 1997;Mortola and Seifert, 2000;Seifert and Mortola, 2002a;Seifert and Mortola, 2002b). In humans, however, the ventilatory response to hypercapnia was higher in the day and was independent of metabolism or sleep Mortola and Seifert, 2002;Mortola, 2004), indicative of an endogenous daily cycle in chemosensitivity.…”

“…Endogenous circadian and circannual oscillations in apnea duration could reflect oscillations in metabolic rate (the need to breathe) or in chemoreflex sensitivity (the drive to breathe). Chemoreflexes are thought to be important in initiating and terminating periods of apnea (Shelton et al, 1986;Milsom, 1990), but the few studies of circadian and circannual variation in chemoreflex responses, performed in mammals and amphibians, have not always observed rhythms in chemoreflex sensitivity (McArthur and Milsom, 1991;Milsom et al, 1993;Peever and Stephenson, 1997;Rocha and Branco, 1998;Bicego-Nahas and Branco, 1999;Mortola and Seifert, 2000;Stephenson et al, 2000;Bicego-Nahas et al, 2001;Mortola and Seifert, 2002;Seifert and Mortola, 2002a;Seifert and Mortola, 2002b;Mortola, 2004).…”